免疫球蛋白和自身抗体在乙型肝炎肝硬化发病和进展中的表达及与预后的关系

The role of immunoglobulin and autoantibodies in the pathogenesis and progression of hepatitis B cirrhosis and their correlation with prognosis

摘要:

目的 探究免疫球蛋白和自身抗体在乙型肝炎（以下简称乙肝）肝硬化发病和进展中的表达及与预后的关系。方法 选取2017年1月—2021年10月成都医学院第二附属医院收治的224例乙肝肝硬化患者，根据Child-Pugh分级，将患者分成Child-Pugh A组（49例）、Child-Pugh B组（119例）和Child-Pugh C组（56例），另取同期在该院体检的健康志愿者作为对照组（60例），比较不同组别受试者免疫球蛋白和自身抗体表达。随访至2022年2月，中位随访时间31个月，失访10例。根据预后情况将患者分成预后不良组（71例）和预后良好组（143例），比较两组患者免疫球蛋白、抗核抗体和线粒体抗体表达，分析基线资料，多因素Cox回归分析预后不良的危险因素，绘制受试者工作特征（ROC）曲线分析免疫球蛋白、抗核抗体和线粒体抗体表达对乙肝肝硬化预后不良的诊断效能。结果 Child-Pugh C组免疫球蛋白G（IgG）、免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、抗核抗体阳性率、抗线粒体抗体阳性率高于对照组和Child-Pugh B组、Child-Pugh A组（P <0.05），Child-Pugh B组IgG、IgA、IgM、抗核抗体阳性率、抗线粒体抗体阳性率高于对照组和Child-Pugh A组（P <0.05），Child-Pugh A组IgG、IgA、IgM、抗核抗体阳性率、抗线粒体抗体阳性率高于对照组（P <0.05）。预后良好组和预后不良组患者IgG、IgA、IgM、抗核抗体阳性率和抗线粒体抗体阳性率比较，差异有统计学意义（P <0.05）。多因素Cox回归分析结果表明，IgM ［O^R=1.799（95% CI：1.232，2.626）］、IgA ［O^R=1.685（95% CI：1.143，2.485）］、IgG ［O^R=1.914（95% CI：1.214，3.015）］、抗核抗体阳性［O^R=1.662 （95% CI：1.342，2.058）］、抗线粒体抗体阳性［O^R=1.839（95% CI：1.488，2.272）］是乙肝肝硬化患者预后不良的危险因素（P <0.05）。ROC曲线分析结果显示，血清IgG敏感性为70.42%，特异性为69.93%；血清IgA敏感性为60.56%，特异性为60.14%；血清IgM敏感性为64.79%，特异性为71.33%；抗核抗体敏感性为83.10%，特异性为76.92%；抗线粒体抗体敏感性为80.28%，特异性为70.63%；联合检测的敏感性为81.69%，特异性为79.72%。结论 血清免疫球蛋白、抗核抗体和抗线粒体抗体在乙肝肝硬化发病、进展患者中异常表达，其单独和联合检测均有效预测疾病预后，临床宜根据其进行针对性干预，以控制乙肝肝硬化进程，改善预后。

Abstract:

Objective To explore the role of immunoglobulin and autoantibodies in the pathogenesis and progression of hepatitis B cirrhosis and their correlation with prognosis.Methods A total of 224 patients with hepatitis B cirrhosis admitted to our hospital from January 2017 to October 2021 were selected and divided into Child-Pugh A group (n = 49), Child-Pugh B group (n = 119) and Child-Pugh C group (n = 56) according to Child-Pugh grading. In addition, healthy volunteers who underwent heath checkup in our hospital at the same period were selected as the control group (n = 60). The levels of immunoglobulin and autoantibodies in different groups were compared. The median follow-up duration was 31 months until February 2022, and 10 patients were lost to follow-up. According to the prognosis, the patients were divided into poor prognosis group (n = 71) and good prognosis group (n = 143), and the levels of immunoglobulin, antinuclear antibody and antimitochondrial antibody were compared between the two groups. The baseline data were characterized, multivariable Cox regression analysis was performed to determine the prognostic risk factors, and ROC curve analysis was used to evaluate the diagnostic efficacy of immunoglobulin, antinuclear antibody and mitochondrial antibody for poor prognosis of hepatitis B cirrhosis.Results The levels of IgG, IgA and IgM, and the positive rates of antinuclear antibody and antimitochondrial antibody in the Child-Pugh C group were higher than those in the control group, the Child-Pugh B group and the Child-Pugh A group (P < 0.05). The levels of IgG, IgA and IgM, and the positive rates of antinuclear antibody and antimitochondrial antibody in the Child-Pugh B group were higher than those in the control group and the Child-Pugh A group (P < 0.05). Besides, the levels of IgG, IgA and IgM, and the positive rates of antinuclear antibody and antimitochondrial antibody in the Child-Pugh A group were higher than those in the control group (P < 0.05). There were significant differences in the levels of IgG, IgA and IgM, and the positive rates of antinuclear antibody and antimitochondrial antibody between the poor prognosis group and good prognosis group (P < 0.05). The multivariable Cox regression analysis showed that high levels of IgM [O^R=1.799 (95% CI: 1.232, 2.626) ], IgA [O^R=1.685 (95% CI: 1.143, 2.485) ], and IgG [O^R=1.914 (95% CI: 1.214, 3.015) ], antinuclear antibody positivity [O^R=1.662 (95% CI: 1.342, 2.058) ] and antimitochondrial antibody positivity [O^R=1.839 (95% CI: 1.488, 2.272) ] were risk factors for poor prognosis of hepatitis B cirrhosis patients (P < 0.05). The ROC curve analysis revealed that the sensitivities of IgG, IgA, IgM, antinuclear antibody, antimitochondrial antibody and their combination for predicting poor prognosis of hepatitis B cirrhosis were 70.42%, 60.56%, 64.79%, 83.10%, 80.28% and 81.69%, with the specificities being 69.93%, 60.14%, 71.33%, 76.92%, 70.63% and 79.72%.Conclusions Serum immunoglobulin, antinuclear antibody and antimitochondrial antibody are abnormally expressed in the pathogenesis and progression of hepatitis B cirrhosis. The immunoglobulin, antinuclear antibody and antimitochondrial antibody alone and their combination are all effective for predicting the poor prognosis of hepatitis B cirrhosis. Thus, clinical intervention targeting the immunoglobulin and autoantibodies could be carried out to control the progression of hepatitis B cirrhosis and to improve the prognosis.